BackBhopal tests raise questions on credibility of India’s clinical trials
Bhopal tests raise questions on credibility of India’s clinical trials
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New Delhi: India has been emerging as a hub for global clinical trials that are key to proving the effectiveness of any new drug. Such extensive testing and research are needed before the findings can be considered conclusive enough by regulators such as the US Food and Drug Administration (FDA) before the drug goes on sale.
But when such drugs are tested on patients exposed to methyl isocyanate (MIC) and the data is mixed together with findings from people who haven’t had such exposure, the research becomes questionable, apart from showing the country’s booming clinical trials’ industry in poor light.
MIC was responsible for the deaths of thousands of people in the Bhopal gas leak in 1984. The debilitating effects of the gas persist among the survivors, which is why the Bhopal Memorial Hospital and Research Centre (BMHRC) was set up in August 2004.
Why was this unique facility even approved as a site for multi-centre clinical trials? Authorities have no simple answer. “The drug controller should have rejected the proposal at the approval stage itself as the patient pool at BMHRC is unique," said Dr C.M. Gulati, an expert on the rational use of drugs and the editor of Monthly Index of Medical Specialities.
“These patients are already on multi-drug therapy for treatment of MIC-related ailments."
Gulati said the Bhopal trials were “bogus" and a reflection of the sloppy manner in which the booming clinical trials industry in India was functioning.
The centre was a part of 13 such trials, with none focusing on the effects of the gas, raising questions about the regulation and approval process for the testing, besides bringing the quality of research in India under a cloud. It didn’t help that 14 patients died in the 13 clinical trials at BMHRC. There is nothing to suggest, however, that the trials had anything to do with the deaths.
While no research has conclusively proven the effects of MIC in the past 27 years, it is then scientifically impossible to prove the effect of another untested trial drug on the gas victims, Gulati said.
He said research in disaster areas usually focuses on how to cope with similar events in the future. Such centres can’t be used for non-specific, commonly used drugs, such as those to treat pneumonia and abdominal infections, as was the case in Bhopal.
“This just goes to show that pharmaceutical companies are looking for willing institutions with large patient pools without any thought to the drug being tested and the patients being chosen," Gulati said.
That’s because drugs tested on them and the data that results will be irrelevant to those not exposed to MIC since the gas victims have undergone genetic changes and progressive damage due to their exposure to the gas.
Findings from multi-centre trials are collated and submitted to regulating authorities such as FDA, the European Medicines Agency and the Medicines and Healthcare Products Regulatory Agency of the UK. The final findings are endorsed by the sponsoring pharmaceutical company before marketing the drugs.
According to the Good Clinical Practice guidelines that govern such tests, the study protocol must mention whether trial participants are already on multi-drug therapy for existing diseases prior to enrolling.
“There can be no compromise of the Good Clinical Practice guidelines or the procedure of acquiring informed consents from trial participants," said Dr Ambrish Mithal, chairman and head of the department of endocrinology at Medanta-The Medicity in Gurgaon. “Most of all, it is inexcusable if there is a grey area in patient profiling. In cases where the patient is exposed to other diseases—and is on a drug therapy for those diseases—it needs to explicitly be stated in the study protocol."
The drug on which trials were conducted at BMHRC included telavancin (for US firm Theravance Inc.), tigecycline (for Wyeth, now part of Pfizer Inc.), prasugrel (for Ranbaxy Laboratories Ltd) and fondaparinux (for GlaxoSmithKline Plc, or GSK) and a fixed-dose combination of cefoperazone with sulbactam, or Magnex, sold by Pfizer in India. While cefoperazone is no longer marketed in the US, its fixed-dose combination with sulbactam that was tested at BMHRC was never approved for use by FDA.
Both Pfizer and GSK said the trials were conducted in line with international standards and with permission from regulatory authorities.
However, according to the audits conducted at BMHRC by the Drug Controller General of India, MIC’s role was not researched in any of the trials.
GSK’s release with regard to the study on Arixtra, the trade name of fondaparinux, said that the company’s role was to analyse the results of the study once it was completed, again failing to mention the role of MIC being studied in the trials. Despite repeated attempts to reach them, Theravance, Quintiles (the contract research organization) and drug controller Dr V.G. Somani were not available for comment.
Dr V.M. Katoch, director general of the Indian Council of Medical Research (ICMR), defended the quality of trials in the country.
“The quality of Indian clinical trials is reliable and we are building strong regulations to plug the loopholes that currently exist in the system," he said.
Katoch also gave a clean chit to BMHRC officials, pharmaceutical companies as well as the contract research organizations involved, adding that issues related to Bhopal tended to get distorted because of strong emotions engendered by the gas disaster and its aftermath.
“A lot of issues raised by people in Bhopal are emotional and the anger on the streets spills over onto all related matters," he said. “There is very little wrongdoing in the clinical trials as I have already mentioned in a reply to a question raised in Parliament. People have a lot of pent-up anger against the Centre and the state government, which is directed to all issues, whether relevant or not."
The draft guidelines on compensation for research-related injuries in India will be one of the ways in which the loopholes that Katoch cited are to be plugged. While the recommendations made by ICMR on the issue have been with the organization and the Union health ministry since 2008, they were sought to be rushed through at the end of last year, with a 31 December, deadline for finalizing the norms.
“We are aware of the social reality and even though there is little wrongdoing in the majority of clinical trials, these laws in the pipeline will plug loopholes in the system," Katoch said.
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